Characterization of epidermal growth factor receptor induction by retinoic acid in a chemically transformed rat liver cell line.
Levels of epidermal growth factor (EGF) receptor expression vary widely among cell lines derived clonally from a chemically transformed population of rat liver epithelial cells. Retinoic acid (RA), a derivative of vitamin A that stimulates differentiation in a number of embryonal cell lines, increases the level of 125I-EGF binding in several clones of the transformed cell lines. One such cell line, GP6ac, which reverts to a less transformed phenotype when treated with RA, exhibited a 3-4-fold increase in surface EGF receptors with prolonged (2-5-day) RA exposure. The increase persisted as long as the cells were treated with RA. The increase in surface EGF receptors was due to induction of receptor biosynthesis, which occurred within 4 h at both the mRNA and protein levels and persisted until the RA was withdrawn. Paradoxically, the RA response was accompanied by an initial 40-50% decrease in 125I-EGF binding during the first 12 h of RA treatment. The decrease was due primarily to a reduction of receptor affinity. Since the phorbol ester 12-O-tetradecanoylphorbol-13-acetate also decreases 125I-EGF binding and increases EGF receptor biosynthesis in GP6ac cells, we tested the effect of RA in cells depleted of protein kinase C by prolonged treatment (18 h) with 10 microM 12-O-tetradecanoylphorbol-13-acetate. The absence of protein kinase C did not affect the induction of receptor mRNA and protein or the decrease in binding during the early period of RA exposure. This indicates that RA induction of EGF receptor synthesis in GP6ac cells involves signaling pathways distinct from those utilized by phorbol esters.(ABSTRACT TRUNCATED AT 250 WORDS)
Raymond
V W
VW
Lineberger Cancer Research Center, University of North Carolina, Chapel Hill 27599.
Grisham
J W
JW
Earp
H S
HS
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004847:Epithelial Cells; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D008769:Methylnitronitrosoguanidine; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*
D012333:RNA, Messenger; D008769:Methylnitronitrosoguanidine; D014212:Tretinoin; D004815:Epidermal Growth Factor; D003513:Cycloheximide; D066246:ErbB Receptors; D013755:Tetradecanoylphorbol Acetate